PDBsum entry 2vxr

Toxin

PDB id: 2vxr

Contents

Protein chain

428 a.a. *

Ligands

SO4 ×3

GOL ×2

Waters ×430

* Residue conservation analysis

PDB id:

2vxr

Name:

Toxin

Title:

Crystal structure of the botulinum neurotoxin serotype g binding domain

Structure:

Botulinum neurotoxin type g. Chain: a. Fragment: binding domain, residues 863-1297. Synonym: bont/g, bontoxilysin-g. Engineered: yes

Source:

Clostridium botulinum. Organism_taxid: 1491. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

1.90Å R-factor: 0.159 R-free: 0.196

Authors:

P.Stenmark,J.Dupuy,R.C.Stevens

Key ref:

P.Stenmark et al. (2010). Crystal structure of the botulinum neurotoxin type G binding domain: insight into cell surface binding. J Mol Biol, 397, 1287-1297. PubMed id: 20219474

Date:

08-Jul-08 Release date: 07-Jul-09

Protein chain

Q60393  (BXG_CLOBO) -  Botulinum neurotoxin type G from Clostridium botulinum

Seq: 1297 a.a.

Struc: 428 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.24.69 - bontoxilysin.
• Reaction: Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on small molecule substrates.
• Cofactor: Zn(2+)

J Mol Biol 397:1287-1297 (2010)

PubMed id: 20219474

Crystal structure of the botulinum neurotoxin type G binding domain: insight into cell surface binding.

P.Stenmark, M.Dong, J.Dupuy, E.R.Chapman, R.C.Stevens.

ABSTRACT

Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-A X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent.